Serabjit-Singh C J, Albro P W, Robertson I G, Philpot R M
J Biol Chem. 1983 Nov 10;258(21):12827-34.
Isozyme-specific enzymatic activities, radial immunodiffusion, and Western blotting were used to study the effects of phenobarbital, Aroclor 1260, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on microsomal levels of cytochrome P-450 forms 2, 5, and 6. The pulmonary concentration of form 2 was decreased to trace levels by the administration of Aroclor 1260 but not TCDD; co-administration of phenobarbital did not mitigate the decrease. The pulmonary concentration of form 5 was not significantly changed following treatment with Aroclor 1260, phenobarbital, or TCDD. The pulmonary content of form 6 was increased 5- and 10-fold by administration of Aroclor 1260 and TCDD, respectively, and decreased 2-fold by treatment with phenobarbital. Further, phenobarbital antagonized the induction of form 6 by Aroclor 1260 but not by TCDD. In the liver, increases and decreases in form 2-mediated benzphetamine N-demethylation were observed following treatment with Aroclor 1260 depending on the time after dose and individual rabbit response. Hepatic induction of form 2 by phenobarbital was significantly decreased by co-administration of Aroclor 1260. However, form 5 was induced in the liver by either Aroclor 1260 or phenobarbital or both. Thus, the effect of Aroclor 1260 on the control of the concentration of form 2 is independent of that of form 5 in the lung and liver. Fractionation of the Aroclor 1260 to remove co-planar polychlorinated biphenyls and dibenzofurans was useful in demonstrating that the pulmonary induction of form 6 was dependent on these components and unrelated to the repression of form 2 in the lung and liver. The apparent repressive effect of phenobarbital on form 6 in the lung is interesting as it suggests an interaction between phenobarbital and polycyclic hydrocarbon-mediated induction.
采用同工酶特异性酶活性、放射免疫扩散法和蛋白质印迹法，研究苯巴比妥、多氯联苯混合物Aroclor 1260和2,3,7,8-四氯二苯并对二恶英（TCDD）对细胞色素P-450 2、5和6型微粒体水平的影响。给予Aroclor 1260后，2型的肺浓度降至痕量水平，但给予TCDD后未出现此情况；同时给予苯巴比妥并不能减轻这种降低。用Aroclor 1260、苯巴比妥或TCDD处理后，5型的肺浓度没有显著变化。给予Aroclor 1260和TCDD后，6型的肺含量分别增加了5倍和10倍，而用苯巴比妥处理后则降低了2倍。此外，苯巴比妥可拮抗Aroclor 1260对6型的诱导作用，但不能拮抗TCDD对6型的诱导作用。在肝脏中，给予Aroclor 1260后，根据给药后的时间和个体兔子的反应，观察到2型介导的苄非他明N-脱甲基作用有所增加或降低。同时给予Aroclor 1260可显著降低苯巴比妥对肝脏中2型的诱导作用。然而，Aroclor 1260或苯巴比妥或两者均可诱导肝脏中的5型。因此，Aroclor 1260对2型浓度的调控作用在肺和肝脏中独立于5型。对Aroclor 1260进行分馏以去除共平面多氯联苯和二苯并呋喃，有助于证明6型的肺诱导作用取决于这些成分，且与肺和肝脏中2型的抑制作用无关。苯巴比妥对肺中6型的明显抑制作用很有趣，因为这表明苯巴比妥与多环烃介导的诱导作用之间存在相互作用。
